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Drug Profiles:
Fluoxetine, AKA Prozac®

CAUTION: Federal law prohibits dispensing without prescription.

prozac


What is Fluoxetine-
Prozac®

okhandFluoxetine also known as Prozac®, is used as a second line preventive treatment for Migraine and some types of headaches. This is not proved very effective but is a good and safe regiment to try if your doctor thinks it my be helpful. Keep records of your Migraine frequency and duration to evaluate if there is any gain after three months. If none-is noted, than work with your doctor to cease and turn to another more helpful preventive medication.

   
Description:

Fluoxetine is the most widely prescribed antidepressant in the US. It is the prototype of the selective serotonin reuptake inhibitors (SSRIs) and has the longest half-life of all the SSRIs. The SSRIs are structurally distinct from the other classes of antidepressants (e.g., monoamine oxidase inhibitors and tricyclics). Fluoxetine was originally approved by the FDA in December 1987 for the treatment of major depression and was subsequently approved February 1994 for use in obsessive-compulsive disorder (OCD). In November 1994, Eli Lilly & Co., withdrew a NDA for a higher-dosage form of fluoxetine (e.g., Lovan) for the treatment of obesity. In November 1996, the FDA approved the use of fluoxetine in the treatment of bulimia nervosa, the first drug to be approved for this condition. The levo-isomer of fluoxetine is currently undergoing continuing investigation for preventive treatment of Migraine. Other uses of fluoxetine have included the treatment of premenstrual syndrome/dysphoric disorder (PMS), ethanol dependence, anorexia nervosa, borderline personality disorder, and panic disorder.


Mechanism of Action:

The precise action of SSRIs is not fully understood, but it is believed that the most important effect is the enhancement of the actions of serotonin due to highly specific serotonin reuptake blockade at the neuronal membrane. SSRIs have less sedative, anticholinergic, and cardiovascular effects than do the tricyclic antidepressant drugs due to dramatically decreased binding to receptors of histamine, acetylcholine, and norepinephrine. Monoamine oxidase is not inhibited by any of the SSRIs. Anticholinergic activity is virtually absent. Fluoxetine is metabolized to norfluoxetine which is also active.


Pharmacokinetics:

Fluoxetine is administered orally and is well absorbed from the GI tract. The presence of food can delay the rate of absorption, but not the extent. There may be some first-pass metabolism. Peak plasma concentrations occur in 6–8 hours. Steady-state plasma concentrations of fluoxetine and its principal active metabolite norfluoxetine are achieved in 2–4 weeks. Both fluoxetine and the active metabolite, norfluoxetine, exist as enantiomers. Since these four compounds differ in kinetics and potency, no relationship between serum concentrations and clinical effect has been defined. Fluoxetine is highly protein-bound (94.5%) to predominantly alpha1-acid glycoprotein. The drug is well distributed, and it readily crosses the blood-brain barrier and presumably the placenta. It is distributed into breast milk.

Fluoxetine is demethylated in the liver to several metabolites. The only known active metabolite is norfluoxetine, which appears to be as effective as its parent in the blockade of serotonin reuptake. Fluoxetine has the slowest elimination of the SSRIs. The half-life of fluoxetine is 2–3 days and that of norfluoxetine is 7–9 days. There is considerable individual variation, which may be associated with rates of N-demethylation and hydroxylation. About 60% of an oral dose is excreted in urine within 35 days, and about 12% of the dose is excreted in the feces within 28 days. Renal impairment does not appear to affect elimination half-lives of the parent drug and its active metabolite. Neither drug is substantially removed by hemodialysis.

 

Other Important (to Migraineurs) Events Observed During Premarketing Evaluation of Prozac (Fluoxetine)-

A footnote regarding Prozac/ Fluoxetine; it was noted to commonly known cause infrequent Migraines from it’s administration. In addition, it was also know to cause rarely cause vascular headaches too, which in turn could trigger more Migraines. During clinical testing in the United States, multiple doses of Prozac were administered to approximately 5,600 subjects. Untoward events associated with this exposure were recorded by clinical investigators using descriptive terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of untoward events into a limited (i.e., reduced) number of standardized event categories.

In the tabulations that follow, a standard COSTART Dictionary terminology has been used to classify reported adverse events. The frequencies presented, therefore, represent the proportion of the 5,600 individuals exposed to Prozac who experienced an event of the type cited on at least 1 occasion while receiving Prozac. All reported events are included except those already listed in Table 1, those COSTART terms so general as to be uninformative, and those events where a drug cause was remote. It is important to note that this information was not presented to you to deter you from using Prozac/ Fluoxetine, but rather point out it should be considered when you and your doctor have excused other more appropriate preventive regimes, particularly those regimes approved by the FDA like Depakote family drug as an example. The follow events where noted.

Events are further classified within the body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are defined as those occurring on 1 or more occasions in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in less than 1/1000 patients.

Body as a Whole--Frequent: chills; Infrequent: chills and fever, cyst, face edema, hangover effect, jaw pain, malaise, neck pain, neck rigidity, and pelvic pain; Rare: abdomen enlarged, cellulitis, hydrocephalus, hypothermia, LE syndrome, moniliasis, and serum sickness.

Cardiovascular System--Infrequent: angina pectoris, arrhythmia, hemorrhage, hypertension, hypotension, Migraine, postural hypotension, syncope, and tachycardia; Rare: AV block first degree, bradycardia, bundle branch block, cerebral ischemia, myocardial infarct, thrombophlebitis, vascular headache, and ventricular arrhythmia.

Digestive System--Frequent: increased appetite; Infrequent: aphthous stomatitis, dysphagia, eructation, esophagitis, gastritis, gingivitis, glossitis, liver function tests abnormal, melena, stomatitis, thirst; Rare: bloody diarrhea, cholecystitis, cholelithiasis, colitis, duodenal ulcer, enteritis, fecal incontinence, hematemesis, hepatitis, hepatomegaly, hyperchlorhydria, increased salivation, jaundice, liver tenderness, mouth ulceration, salivary gland enlargement, stomach ulcer, tongue discoloration, and tongue edema.

Endocrine System--Infrequent: hypothyroidism; Rare: goiter and hyperthyroidism.

Hemic and Lymphatic System--Infrequent: anemia and lymphadenopathy; Rare: bleeding time increased, blood dyscrasia, leukopenia, lymphocytosis, petechia, purpura, sedimentation rate increased, and thrombocythemia.

Metabolic and Nutritional--Frequent: weight loss; Infrequent: generalized edema, hypoglycemia, peripheral edema, and weight gain; Rare: dehydration, gout, hypercholesteremia, hyperlipemia, hypoglycemic reaction, hypokalemia, hyponatremia, and iron deficiency anemia.

Musculoskeletal System--Infrequent: arthritis, bone pain, bursitis, tenosynovitis, and twitching; Rare: bone necrosis, chondrodystrophy, muscle hemorrhage, myositis, osteoporosis, pathological fracture, and rheumatoid arthritis.

Nervous System--Frequent: abnormal dreams and agitation; Infrequent: abnormal gait, acute brain syndrome, akathisia, amnesia, apathy, ataxia, buccoglossal syndrome, CNS stimulation, convulsion, delusions, depersonalization, emotional lability, euphoria, hallucinations, hostility, hyperkinesia, hypesthesia, incoordination, libido increased, manic reaction, neuralgia, neuropathy, paranoid reaction, psychosis, and vertigo; Rare: abnormal electroenthesia, CNS depression, coma, dysarthria, dystonia, extrapyramidal syndrome, hypertonia, hysteria, myoclonus, nystagmus, paralysis, reflexes decreased, stupor, and torticollis.

Respiratory System--Frequent: bronchitis, rhinitis, and yawn; Infrequent: asthma, epistaxis, hiccup, hyperventilation, and pneumonia; Rare: apnea, hemoptysis, hypoxia, larynx edema, lung edema, lung fibrosis/alveolitis, and pleural effusion.

Skin and Appendages--Infrequent: acne, alopecia, contact dermititis, dry skin, herpes simplex, maculopapular rash, and urticaria; Rare: eczema, erythema multiforme, fungal dermititis, herpes zoster, hirsutism, psoriasis, purpuric rash, pustular rash, seborrhea, skin discoloration, skin hypertrophy, subcutaneous nodule, and vesiculobullous rash.

Special Senses--Infrequent: amblyopia, conjunctivitis, ear pain, eye pain, mydriasis, photophobia, and tinnitus; Rare: blepharitis, cataract, corneal lesion, deafness, diplopia, eye hemorrhage, glaucoma, iritis, ptosis, strabismus, and taste loss.

Urogenital System--Infrequent: abnormal ejaculation, amenorrhea, breast pain, cystitis, dysuria, fibrocystic breast, leukorrhea, menopause, menorrhagia, ovarian disorder, urinary incontinence, urinary retention, urinary urgency, urination impaired, and vaginitis; Rare: abortion, albuminuria, breast enlargement, dyspareunia, epididymitis, female lactation, hematuria, hypomenorrhea, kidney calculus, metrorrhagia, orchitis, polyuria, pyelonephritis, pyuria, salpingitis, urethral pain, urethritis, urinary tract disorder, urolithiasis, uterine hemorrhage, uterine spasm, and vaginal hemorrhage.

If you are uncomfortable with using this medication as a preventive sit down with your doctor, present this and other concerns you may have. Then listen to your doctor and if you suffer from a co-morbid condition such as clinical depression, then there would be more merit to following this course.